P51 EFFICACY AND SAFETY OF THIRD-LINE OR LATER TREATMENTS, INCLUDING THE CD38 MONOCLONAL ANTIBODY CLASS, IN PATIENTS WITH RELAPSED/REFRACTORY MULTIPLE MYELOMA: A SYSTEMATIC LITERATURE REVIEW
Authors: M. Hanna, J. Chorazy, I. Iheanacho, B. Gorsh, P.F. Wang, P. Paka, S. Perera
Journal: HemaSphere (2023)

Objectives: There is a need to contextualize treatment outcomes in relapsed/refractory multiple myeloma (RRMM) in light of prior therapies and disease/treatment characteristics. Comparisons across studies are challenging, especially in later lines of RRMM where treatment is highly heterogenous. We conducted a systematic literature review exploring efficacy and safety outcomes across approved and investigational agents in third-line/later (3L+) RRMM treatment and in patients refractory to anti-CD38 antibody therapy. Methods: Searches were conducted on 28 Mar 22 for publications (2008–2022) and grey literature (2018–2020) reporting interventional studies in patients receiving RRMM treatment after ≥2 prior lines of therapy (LOTs). 2 reviewers screened the studies without geographical/language restrictions. Results were synthesised descriptively. Results: 147 unique studies met eligibility criteria including 1 randomised controlled trial (RCT)/single-arm trial, 41 RCTs, 87 single-arm trials, 12 non-RCTs and 6 pooled analyses. Median progression-free survival (PFS) and overall survival (OS) varied widely across studies; trial populations also differed substantially regarding potential key treatment outcome modifiers. The shortest median PFS (0.9 months; median follow-up, 23 months) was seen in heavily pretreated patients mostly refractory to lenalidomide (LEN). PFS was longest (≤38.8 months; median follow-up, 44.3 months) in patients who had received as few as 2 prior LOTs and were not LEN-refractory. Median OS ranged from 6.4 months (follow-up not reported) in patients exposed to ≥3 prior LOTs to 54.3 months (median follow-up, 85 months) in patients who had received as few as 2 prior LOTs and were not LEN-refractory. Similarly, overall response rates (ORRs) varied widely from 0% for LEN-refractory patients to 100% for anti-CD38 refractory patients. Among 19 studies reporting data for anti-CD38 refractory patients, most enrolled <50 patients per trial and were Phase I or I/II trials; only 2 were RCTs. 2 trials exclusively included triple-class refractory populations (refractory to ≥1 proteasome inhibitor, an immunomodulatory drug and an anti-CD38 monoclonal antibody). 10 trials included a subset of triple-class refractory patients (65–97% of total populations) and 5 studies enrolled broader populations but provided data for subgroups of triple-class refractory patients. Many studies provided safety/ORR data only; few reported median PFS and/or OS. Where reported, adverse event rates were high (94–100%). Anaemia, thrombocytopaenia and neutropaenia were most frequently reported considering all 3L+ treatments. Conclusions: We identified a large body of data related to 3L+ treatments in RRMM. Considerable heterogeneity in previous treatment exposures, and disease and patient characteristics were observed, along with substantial diversity in outcomes and endpoints reported. Careful consideration of these factors is relevant as the standard of care (SOC) in early LOTs could change, which could impact treatment options for later LOTs. It is challenging to identify a SOC for the 3L+ setting given the evidence observed, particularly due to heterogeneity in populations, subgroups and outcomes. Treatment choice could therefore be dictated by multiple prognostic and patient characteristics. A network meta-analysis that considers these differences could facilitate robust quantitative comparative efficacy and safety evaluations for RRMM treatment options.